Locally-advanced periocular basal cell carcinoma (BCC) pose many therapeutic challenges due to the need to preserve functionality and cosmesis of the orbit and periocular area. Surgical excision and subsequent orbital exenteration are two recognized modalities of treatment. Vismodegib is currently an FDA-approved monotherapy for locally-advanced and metastatic BCC. We present a case of the use of vismodegib as neoadjuvant therapy prior to surgical excision of a locally-advanced periocular recurrent BCC in a 75-year-old male. The patient’s tumor successfully responded to vismodegib allowing surgical excision with clear margins. The orbit was saved in a patient who otherwise would have required complete orbital exenteration. J Drugs Dermatol. 20(5):552-554. doi:10.36849/JDD.5661.